What is an investigational drug?
An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.
What is vicriviroc?
Vicriviroc is an investigational drug that was studied for the treatment of HIV infection. In 2010, the study of vicriviroc for HIV treatment was discontinued.3
Currently, vicriviroc-containing topical microbicides to prevent sexual transmission of HIV infection in women are being studied in early clinical trials.4,5 Topical microbicides are products that are applied to the vagina or rectum (such as gels, films, or creams) or inserted into the vagina (such as vaginal rings) to prevent getting STIs, such as HIV infection.6,7
Vicriviroc belongs to a class (group) of HIV drugs called entry and fusion inhibitors.2 Entry and fusion inhibitors block HIV from getting into and infecting certain cells of the immune system. This prevents HIV from multiplying and can reduce the amount of HIV in the body.
Vicriviroc works by attaching to one of two proteins on the surface of the immune cells. These proteins are called the CCR5 and CXCR4 co-receptors. Vicriviroc attaches to the CCR5 co-receptor. When vicriviroc attaches to the CCR5 co-receptor, certain strains of HIV—called R5-tropic virus—cannot attach to, enter, or infect the cell.8
How are clinical trials of investigational drugs conducted?
Clinical trials are conducted in “phases.” Each phase has a different purpose and helps researchers answer different questions.9
- Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
- Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
- Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.9
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase III clinical trial
to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials
to seek more information about the drug’s risks, benefits, and optimal use.9
In what phase of testing is vicriviroc?
Vicriviroc for HIV treatment has been studied in Phase III clinical trials.2 The development of vicriviroc for the treatment of HIV infection was discontinued in July 2010.3
Vicriviroc-containing topical microbicides to prevent sexual transmission of HIV infection in women are currently being studied in Phase I clinical trials.4,5
What are some studies on vicriviroc?
Note: The study of oral vicriviroc for HIV treatment was discontinued in 2010. The company developing the drug announced that this decision was based on data from one Phase II trial in treatment-naive adults and two Phase III trials in treatment-experienced adults. In these trials, vicriviroc failed to show improved efficacy over currently approved HIV medicines already in use.3,10,11
Study Names: P04875; NCT00551018
Location: This study was conducted globally.
Participants: HIV-infected adults who had never taken HIV medicines before entering the study (also called treatment-naive). All participants were infected with R5-tropic HIV (virus that uses CCR5 as a coreceptor).
Purpose: The purpose of this study was to compare vicriviroc taken once daily versus the FDA-approved combination drug emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada).
Study Design: Participants were randomly assigned to receive either 30 mg of vicriviroc or Truvada, each taken once daily and orally. All participants also received a background regimen containing the FDA-approved protease inhibitors atazanavir (brand name: Reyataz) and ritonavir (brand name: Norvir). (A background regimen is a combination of drugs that are not being studied as the investigational drug[s] in the clinical trial, but are being given to help control a participant’s HIV infection.)
- The vicriviroc regimen had similar anti-HIV activity as the Truvada regimen. Anti-HIV activity was measured as a drop in viral load (the amount of HIV in a blood sample) from the time of study entry to Week 48.
- In terms of efficacy, vicriviroc did not appear to work as well as Truvada. Efficacy was measured as the proportion of participants in each treatment group that had a viral load less than 50 copies/mL at Week 48.
- In terms of safety, more participants in the vicriviroc group discontinued the study because of side effects than in the Truvada group.11,12
: 1) VICTOR-E3; NCT00523211; P04405AM5 and 2) VICTOR-E4; NCT00474370; P04889AM8
: North and South America, Europe, and South Africa
: HIV-infected adults who had taken HIV medicines before entering the study (also called treatment-experienced). All participants were infected with R5-tropic HIV.
: The purpose of the studies VICTOR-E3 and VICTOR-E4 was to compare the safety and effectiveness of vicriviroc versus placebo
. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.)
: Participants in each study were randomly assigned to receive either 30 mg of vicriviroc or placebo, each taken once daily and orally.
All participants also received an optimized background regimen. (An optimized background regimen is a combination of drugs, chosen on the basis of a person’s resistance test results and treatment history, that are not being studied as the investigational drug[s] in the clinical trial, but are given to help control a participant’s HIV infection.) Participants’ background regimens contained a protease inhibitor
boosted by ritonavir plus two fully active antiretroviral
involves the use of a second drug to increase the effectiveness of the main [first] drug.)
- In a combined analysis of VICTOR-E3 and VICTOR-E4, vicriviroc plus optimized background therapy did not work any better than placebo plus optimized background therapy after 48 weeks of treatment. The majority of study participants were receiving at least three active drugs as part of their optimized background regimens.
- In an analysis of study participants receiving two or fewer active drugs in their background regimens, vicriviroc proved to be more effective than placebo.
- In terms of safety, vicriviroc was comparable to placebo. However, more participants in the vicriviroc groups dropped out of the study because of a side effect than in the placebo groups.10,13-15
Vicriviroc is currently being developed into topical microbicide
products to prevent sexually acquired HIV infection in women. Two Phase I studies will be looking at the safety and drug properties of intravaginal
rings (IVRs) containing vicriviroc.4,5
In one of the Phase I studies (NCT02356302), investigators will evaluate (1) an IVR containing vicriviroc (2) an IVR containing MK-2048 (an investigational integrase
inhibitor) and (3) a combination IVR containing both vicriviroc and MK-2048. (The combination IVR is also known as MK-2048A.) Each of the three IVRs will be compared to a placebo IVR.4
The other Phase I study (NCT02419456) will be looking at the combination IVR (MK-2048A) at two different dose
What side effects might vicriviroc cause?
In the Phase III studies discussed under the previous question (VICTOR-E3 and VICTOR-E4), side effects were similar in both the vicriviroc and placebo groups. The vicriviroc group had a greater percentage of participants stopping the study because of side effects than the placebo group did.10,13
In the Phase II study discussed under the previous question (NCT00551018), no common adverse events were seen in the vicriviroc group. More vicriviroc than Truvada participants discontinued the study because of side effects.11
Clinical trials of intravaginal rings containing vicriviroc are just beginning. When these studies are completed and if new studies are conducted, information on possible side effects of vaginal rings containing vicriviroc will be gathered.
Where can I get more information about clinical trials studying vicriviroc?
More information about vicriviroc-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.
I am interested in participating in a clinical trial of vicriviroc. How can I find more information about participating in a clinical trial?
Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.8
Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/306296-47-9. Last accessed on October 15, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on October 15, 2015.
- Dunkle LM. Merck Research Laboratories. Vicriviroc Discontinued Investigator Letter. National AIDS Treatment Advocacy Project (NATAP): News Updates; 2010. Available at: http://www.natap.org/2010/newsUpdates/071510_02.htm. Last accessed on October 15, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID). Phase 1 Safety and Pharmacokinetics Study of MK-2048/Vicriviroc (MK-4176)/MK-2048A Intravaginal Rings. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 2, 2015. NLM Identifier: NCT02356302. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02356302. Last accessed on October 15, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID). Phase 1 Pharmacokinetic Trial of Two Intravaginal Rings (IVRs) Containing Different Dose Strengths of Vicriviroc (MK-4176) and MK-2048. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 14, 2015. NLM Identifier: NCT02419456. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02419456. Last accessed on October 15, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID Research on Topical Microbicides. Available at: http://www.niaid.nih.gov/topics/hivaids/research/prevention/pages/topicalmicrobicides.aspx. Last accessed on October 15, 2015.
- Shattock RJ, Rosenberg Z. Microbicides: Topical Prevention against HIV. Cold Spring Harb Perspect Med. 2012 Feb;2(2):a007385. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281595/. Last accessed on October 15, 2015.
- Strizki JM, Tremblay C, Xu S, et al. Discovery and Characterization of Vicriviroc (SCH 417690), a CCR5 Antagonist with Potent Activity against Human Immunodeficiency Virus Type 1. Antimicrob Agents Chemother. 2005 Dec;49(12):4911-19. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1315929/. Last accessed on [posting date].
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on October 15, 2015.
- Caseiro MM, Nelson M, Diaz RS, et al. Vicriviroc plus optimized background therapy for treatment-experienced subjects with CCR5 HIV-1 infection: final results of two randomized phase III trials. J Infect. 2012 Oct;65(4):326-35. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22634184. Last accessed on October 15, 2015.
- Dunkle LM, Gathe J, Zhou H, McCarthy M. Antiviral Effect of Vicriviroc (VCV) plus Ritonavir-Boosted Atazanavir (ATV/r) Similar to Tenofovir/emtricitabine (TEM) + ATV/r but Efficacy (%<50c/mL) Inferior as Initial Therapy. Abstract presented at: 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12-15, 2010; Boston, MA. Abstract H-938a. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=d89fb4da-4268-4d6b-88ee-4f4ebcd548de&cKey=bb11cf2f-7e42-4aa1-bffa-d364f8cc3e6d&mKey=%7b93AEED6A-54D4-4EF6-99BD-A9B3CE9FACD9%7d. Last accessed on October 15, 2015.
- Merck Sharp & Dohme Corp. Efficacy and Safety of VICRIVIROC in HIV-Infected Treatment-Naïve Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 29, 2007. NLM Identifier: NCT00551018. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00551018. Last accessed on October 15, 2015.
- Mascolini M. Vicriviroc Does Not Outdo Placebo Regimen in Phase 3 Trials. Conference Reports for National AIDS Treatment Advocacy Project (NATAP): 17th Conference on Retroviruses and Opportunistic Infections (CROI); February 16-19, 2010; San Francisco, CA. Available at: http://www.natap.org/2010/CROI/croi_12.htm. Last accessed on October 15, 2015.
- Merck Sharp & Dohme Corp. Vicriviroc in Combination Treatment With an Optimized ART Regimen in HIV-Infected Treatment-Experienced Subjects (VICTOR-E3). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 30, 2007. NLM Identifier: NCT00523211. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00523211. Last accessed on October 15, 2015.
- Merck Sharp & Dohme Corp. Vicriviroc in Combination Treatment With an Optimized ART Regimen in HIV-Infected Treatment-Experienced Subjects (VICTOR-E4). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 15, 2007. NLM Identifier: NCT00474370. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00474370. Last accessed on October 15, 2015.
Last Reviewed: October 19, 2015